Magnolol alleviates high-fat diet-induced steatosis, inflammation and fibrosis in obesity-associated liver injuries via MOGAT1-mediated lipid metabolism and NF-κB signaling

Background Magnolol (MAG), a bioactive compound from Magnolia officinalis, possesses anti-inflammatory and lipid-lowering properties, but its role in obesity-associated liver injury and its molecular targets remain unknown. Methods High-fat diet (HFD)-fed mice were treated with MAG (10 or 20 mg/kg) daily for 7 days. AML12 hepatocytes were challenged with PA with or without MAG pretreatment. Liver injury was evaluated by histology, serum biochemistry, qPCR and Western blot. RNA-seq and mechanistic studies were performed to identify MAG-regulated pathways and targets. Results MAG significantly reduced hepatic lipid accumulation, serum transaminases, and collagen deposition in HFD-fed mice. RNA-seq identified monoacylglycerol O-acyltransferase 1 (MOGAT1) as the most significantly downregulated lipogenic gene by MAG. MOGAT1 expression correlated positively with liver triglyceride and injury markers. MAG also suppressed HFD-induced NF-κB activation (reduced P65 phosphorylation and nuclear translocation, lower IL-6, TNF-α, IL-1β). These findings were recapitulated in PA-treated AML12 cells. Critically, MOGAT1 overexpression largely reversed MAG-mediated suppression of inflammatory and fibrotic responses, demonstrating a causal role of MOGAT1 in MAG’s protective effects. Conclusion MAG alleviates HFD-induced hepatic steatosis, inflammation and fibrogenic responses by suppressing MOGAT1-mediated triglyceride synthesis and subsequent NF-κB-driven inflammation. This study identifies MOGAT1 as a novel downstream effector and functional mediator of MAG, providing new mechanistic insight into its hepatoprotective action and supporting its therapeutic potential for obesity-associated liver injuries.